P,N,N-Pincer nickel-catalyzed cross-coupling of aryl fluorides and chlorides

Article abstract of DOI:10.1039/c4ob01041h

P,N,N-Pincer nickel complexes [Ni(Cl){N(2-R₂PC₆H ₄)(2′-Me₂NC₆H₄)}] (R = Ph, 3a; R = Prⁱ, 3b; R = Cy, 3c) were synthesized and their catalysis toward the Kumada or Negishi cross-coupling reaction of aryl fluorides and chlorides was evaluated. Complex 3a effectively catalyzes the cross-coupling of (hetero)aryl fluorides with aryl Grignard reagents at room temperature. Complex 3a also catalyzes the cross-coupling of (hetero)aryl chlorides and arylzinc reagents at 80 °C with low catalyst loadings and good functional group compatibility. the Partner Organisations 2014.

Full text of DOI:10.1039/c4ob01041h

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P,N,N-Pincer nickel-catalyzed cross-coupling of
aryl fluorides and chlorides†
Cite this: Org. Biomol. Chem., 2014,
12, 6414
Dan Wu and Zhong-Xia Wang*
P,N,N-Pincer nickel complexes [Ni(Cl){N(2-R2PC6H4)(2’-Me2NC6H4)}] (R = Ph, 3a; R = Pri, 3b; R = Cy, 3c)
were synthesized and their catalysis toward the Kumada or Negishi cross-coupling reaction of aryl
fluorides and chlorides was evaluated. Complex 3a effectively catalyzes the cross-coupling of (hetero)aryl
fluorides with aryl Grignard reagents at room temperature. Complex 3a also catalyzes the cross-coupling
of (hetero)aryl chlorides and arylzinc reagents at 80 °C with low catalyst loadings and good functional
group compatibility.
Received 20th May 2014,
Accepted 30th June 2014
DOI: 10.1039/c4ob01041h
www.rsc.org/obc
Introduction
Transition-metal-catalyzed cross-coupling reactions are power-
ful tools to construct new C–C bonds. Nucleophiles used in
these cross-couplings include various organometallic reagents
such as organo-magnesium, -zinc, -tin, -boron, and -silicon
compounds.1,2 In the earlier stage of the study organoiodides
and bromides were predominately employed as the
electrophiles.1–3 In the last 15 years organochlorides as the
electrophiles were extensively explored because of their lower
cost and the diversity of available compounds.4 However, the
use of chlorides as electrophiles has proven more difficult due
to the low reactivity of the C–Cl bond. Hence developing highly
active catalyst systems is an important research topic.5 Cross-
coupling using organofluorine compounds as electrophiles
also attracted considerable attention in recent years. The C–F
bond is known as the strongest single bond to carbon. It is
very challenging to cut off such a bond and helpful for the fun-
damental understanding of the reactivity of very stable bonds.6
On the other hand, it is one of the effective ways to prepare
partially fluorinated compounds from poly- or perfluorinated
species.6d,7 Some catalysts for the activation of organochlor-
ides or fluorides have been reported, including palladium,
nickel, copper, cobalt, iron and other transition metal com-
plexes. However, investigations of highly active and widely
applicable catalysts are still attractive. Pincer nickel complexes
Chart 1 N,N,N-, P,N,P- and P,N,N-pincer nickel complexes.
have been proven to catalyze cross-couplings of organohalides
including chlorides and fluorides with various nucleo-
philes.5o–r,8 Among the pincer nickel complexes with catalytic
activity, we noticed that N,N,N-pincer nickel complex
1
(Chart 1) can efficiently catalyze Kumada coupling of β-hydro-
gen-containing nucleophiles or electrophiles.9 P,N,P-Pincer
nickel complexes 2a–2c (Chart 1) can catalyze Kumada coup-
ling of phenyl iodide or bromide with aryl or alkyl Grignard
reagents.10 A P,N,N-pincer ligand with similar skeletal struc-
ture to those in 1 and 2 will provide a different coordination
environment and its nickel complexes may exhibit different
catalytic properties from 1 and 2. Hence we synthesized P,N,N-
pincer nickel complexes 3a–3c (Chart 1) and examined their
catalytic action. The study showed that complex 3a effectively
catalyzes cross-couplings of aryl fluorides with aryl Grignard
reagents and aryl chlorides with arylzinc reagents. Herein we
report the results.
CAS Key Laboratory of Soft Matter Chemistry and Department of Chemistry,
University of Science and Technology of China, Hefei, Anhui 230026, People’s
Republic of China. E-mail: zxwang@ustc.edu.cn; Fax: +86 551 63601592;
Tel: +86 551 63603043
†Electronic supplementary information (ESI) available: Details of synthesis and
characterization of complexes 3a–3c; details of single crystal X-ray diffraction
determination of complex 3c. Copies of 1H and 13C NMR spectra of the cross-
coupling products. CCDC 996222. For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/c4ob01041h
Results and discussion
Synthesis of complexes 3a–3c is summarized in Scheme 1 and
the experimental details are provided in the ESI.†
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Table 1 Evaluation of catalytic activity of complexes 3a–3c in the
Kumuda reactiona
Entry
Cat. (mol%)
Solvent
Yieldb (%)
1
2
3
4
5
6
7
3a (1)
3b (1)
3c (1)
3a (1)
3a (1)
3a (0.5)
3a (0.5)
THF
THF
THF
Et2O
Toluene
Et2O
Toluene
46
24
34
82
90
84
87
Scheme 1 Synthesis of complexes 3a–3c.
a The reaction was carried out according to the conditions indicated
by above equation; 0.5 mmol p-FC6H4OMe and 0.75 mmol
p-MeC6H4MgBr were employed. b Isolated yield.
toluene, giving 82% and 90% product yields, respectively
(entries 4 and 5, Table 1). The reaction using 0.5 mol% of 3a
afforded the corresponding product in 84% yield in Et2O and
87% yield in toluene (entries 6 and 7, Table 1).
It has been reported that catalyst-free nucleophilic aromatic
substitution of aryl fluorides by nitrogen, oxygen, sulfur or
carbon nucleophiles can occur under appropriate conditions,
but usually apply to electron-deficient aryl fluorides.6c In order
to rule out the possibility, we respectively ran the reaction of
fluorobenzene and 2-fluoropyridine with p-MeC6H4MgBr in
toluene at room temperature in the absence of a catalyst. The
results showed that no substitution products were observed in
24 h and the starting materials remained.
The substrate scope of the catalytic reactions was examined
using 3a as the catalyst and toluene as the solvent.
m-FC6H4OMe showed higher reactivity than p-FC6H4OMe. The
former reacted with p-MeC6H4MgBr using 0.5 mol% 3a in
toluene at 25 °C to afford the cross-coupling product in 91%
yield (entry 1, Table 2). However, this small reactivity differ-
Fig. 1 Molecular structure of complex 3c. Selected bond lengths (Å):
Ni1–P1 2.1368(8), Ni1–N1 1.858(2), Ni1–N2 2.006(2), Ni1–Cl1 2.1636(10).
Each of the complexes is a diamagnetic crystalline solid
and was characterized by 1H, 13C and 31P NMR spectroscopy ence between meta- and para-positions of fluorinated anisoles
and elemental analysis. Complex 3c was also characterized by does not allow for selective defluorination in a polyfluoro-
single crystal X-ray diffraction.11 The result showed that the
anisole molecule. For example, reaction of 2,3,4,5,6-pentafluoro-
central nickel atom is coordinated by P1N1N2 and Cl1 atoms anisole with 1 equiv. of p-MeC6H4MgBr under the same
and has an approximate square planar geometry (Fig. 1). The conditions as above resulted in a complicated mixture of
Ni1–N1 distance of 1.858(2) Å is between the corresponding
products. p-FC6H4NMe2 exhibited lower reactivity than
bond distances of complexes 1 and 2b [1.835(2) Å and 1.9030(17) p-FC6H4OMe due to strong electron donating properties of the
Å, respectively].9b,10 The Ni1–N2 distance of 2.006(2) Å is NMe2 group. Its reaction with p-MeC6H4MgBr in the presence
longer than those in complex 1 [1.956(2) and 1.9598(19) Å].9b
of 0.5 mol% 3a afforded the cross-coupling product in 77%
The Ni1–P1 distance of 2.1368(8) Å is shorter than those in yield. However, the reaction using 2 mol% of 3a gave quantitat-
complex 2b [2.1884(6) and 2.1913(6) Å].10
ive amounts of the product (entry 2, Table 2). 4-Fluoro-1,2-
dimethoxybenzene is a very inert electrophile. Its reaction with
Catalytic properties of complexes 3a–3c were evaluated
using reaction of p-MeOC6H4F with p-MeC6H4MgBr in THF. either p-MeC6H4MgBr or p-Me2NC6H4MgBr required higher
The reaction was run at room temperature for 24 h in the pres- reaction temperature (70 °C) and higher catalyst loadings
ence of 1 mol% of 3a, 3b or 3c. Complex 3a resulted in the
(2 mol%), giving the corresponding cross-coupling products in
cross-coupling product in 46% yield, and 3b and 3c led to 24% moderate yields (entries 3 and 4, Table 2). Reaction of 3-(4-
and 34% yields, respectively (entries 1–3, Table 1). The reaction fluorophenyl)-1-isopropyl-1H-indole, (4-fluorophenyl)methanol
was found to proceed more effectively in either Et2O or
and 1-fluoro-2-methylbenzene with p-MeC6H4MgBr or
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Table 2 Cross-coupling of aryl fluorides with ArMgBr catalyzed by 3aa
Table 2 (Contd.)
Ar1
mol% 3a
Yieldb (%)
91
Entry
17
ArF
Ar1
mol% 3a
Yieldb (%)
74g
Entry
1
ArF
p-MeC6H4
1
p-MeC6H4
0.5
18
p-MeC6H4
3
76h
2
3
p-MeC6H4
p-MeC6H4
0.5
2
77(99c)
54d
a Unless otherwise specified, the reactions were carried out on a
0.5 mmol scale according to the conditions indicated by the above
equation, 0.75 mmol ArMgBr were used. b Isolated yield. c 2 mol%
catalyst loading. d The reaction was carried out at 70 °C. e 1.25 mmol
ArMgBr were used. f The reaction was run in Et2O. g 3 equiv. of ArMgBr
were used. h 4.5 equiv. of ArMgBr were used.
4
5
p-Me2NC6H4
p-MeC6H4
2
66d
91
0.5
p-Me2NC6H4MgBr gave good product yields although the
reaction of (4-fluorophenyl)methanol and 1-fluoro-2-methyl-
benzene required 2 mol% of catalyst loadings (entries 5–7,
Table 2). Reaction of (4-fluorophenyl)methanol also required
more amount of Grignard reagents due to the presence of the
hydroxy group in the molecule. Both fluorobenzene and
1-fluoronaphthalene showed good reactivity in the cross-coup-
ling. Their reactions with p-Me2NC6H4MgBr in the presence
of 0.5 mol% 3a afforded desired products in quantitative
yields. Cross-coupling of 1-fluoro-2-methylbenzene with
p-Me2NC6H4MgBr in the presence of 2 mol% 3a produced
N,N,2′-trimethylbiphenyl-4-amine in 95% yield (entries 8–10,
Table 2). As an electron-poor aryl fluoride, 1-fluoro-4-(trifluoro-
methyl)benzene was expected to be a reactive substrate in the
cross-coupling. However, its reaction with p-MeC6H4MgBr
required 2 mol% catalyst loading and gave only 63% product
yield for unclear reasons (entry 11, Table 2). 2-Fluoropyridine,
2-fluoro-4-methylpyridine and 3-fluoropyridine showed good
reactivity with Grignard reagents including p-MeC6H4MgBr,
p-MeOC6H4MgBr and p-Me2NC6H4MgBr. Each reaction gave
good product yield although reaction of 3-fluoropyridine
required higher catalyst loading (2 mol%) than the others
(entries 12–16, Table 2). Reactions of 1,4-difluorobenzene and
1,3,5-trifluorobenzene were also evaluated. The reaction of the
former with 3 equiv. of p-MeC6H4MgBr in the presence of
1 mol% 3a afforded 1,4-bis(p-tolyl)benzene in 74% yield,
and the latter with 4.5 equiv. of p-MeC6H4MgBr in the pres-
ence of 3 mol% 3a generated 1,3,5-tris(p-tolyl)benzene in 76%
yield (entries 17 and 18, Table 2). Attempts to selectively
prepare a monoarylated product using less amounts of
Grignard reagents under the same conditions were unsuccess-
ful. A mixture of mono- and multi-arylated products was
formed.
6
7
8
9
p-MeC6H4
2
90e
81e
99
p-Me2NC6H4
p-Me2NC6H4
p-Me2NC6H4
2
0.5
0.5
99
10
p-Me2NC6H4
2
95
11
12
p-MeC6H4
p-MeC6H4
2
63
0.5
77(89f)
13
14
15
p-MeOC6H4
p-Me2NC6H4
p-MeC6H4
0.5
0.5
0.5
81
86
86
16
p-MeC6H4
2
81
Nickel, palladium, manganese, titanium, and tantalum
complexes including pincer nickel complexes (e.g. 4 and 5,
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tried and a 2 : 1 mixture of THF and NMP was proven to be the
best one (Table 3). Temperature lower than 80 °C resulted in a
yield decrease (entries 4 and 5, Table 3). In addition, we also
noticed that the zinc reagent, p-MeC6H4ZnCl, prepared from
the corresponding Grignard reagent in the presence of 2 equiv.
of LiCl gave better reaction results than those prepared from
ZnCl2 and p-MeC6H4Li or ZnCl2 and p-MeC6H4MgBr in the
absence of LiCl (entries 10 and 11, Table 3).
Chart 2 Pincer nickel complexes and hydroxyphosphine ligand.
With the optimized reaction conditions in hand, we exam-
ined the scope of electrophiles and nucleophiles (Table 4).
Deactivated m- and o-ClC6H4OMe can also react with
p-MeC6H4ZnCl. However, the reaction of o-ClC6H4OMe was
much more difficult than p- or m-ClC6H4OMe due to its steric
hindrance, higher catalyst loading and higher reaction temp-
erature being required (entries 1 and 2, Table 4). Reaction of
2,5-Me2C6H3Cl with p-Me2NC6H4MgBr also required relatively
high catalyst loading and reaction temperature, giving the
desired product in 95% yield. Reaction of unactivated C6H5Cl
with p-Me2NC6H4ZnCl was very efficient, 0.01 mol% 3a result-
ing in 99% yield of the product. p-MeOC6H4MgBr seems to be
less reactive than p-Me2NC6H4ZnCl in the reaction with
C6H5Cl. The former required 0.1 mol% of catalyst loading and
led to 81% product yield (entries 4 and 5, Table 4). A series
of functionalized aryl chlorides were tested. Reaction of
p-ClC6H4CF3, p-ClC6H4C(O)Ph, p-ClC6H4COOEt and p-ClC6H4-
C(O)NEt2 with p-MeC6H4ZnCl, p-MeOC6H4ZnCl or p-Me2-
NC6H4ZnCl proceeded smoothly in the presence of 0.01 mol%
3a, giving the corresponding cross-coupling products in excel-
lent yields (entries 6–14, Table 4). Reaction of p-ClC6H4CN
required a higher catalyst loading and gave a relatively low
yield (entry 15, Table 4). This is ascribed to the coordination of
the nitrile group with the catalyst species.13 o-ClC6H4C(O)Ph
and o-ClC6H4CN showed lower reactivity compared with the
corresponding para-substituted partners due to steric
hindrance. However, reaction of o-MeC6H4ZnCl with either
deactivated or activated aryl chlorides including p-ClC6H4OMe,
p-ClC6H4C(O)Ph, p-ClC6H4COOEt and p-ClC6H4C(O)NEt2
resulted in excellent product yields (entries 19–22, Table 4).
Several heteroaryl chlorides including 2-chloronicotinonitrile,
2-chloro-6-methoxypyridine and 2-chloro-4-methylquinoline
were also proven to be suitable electrophiles for the coupling.
Reaction of each of them gave excellent yields (entries 23–26,
Table 4). The electron-poor arylzinc reagent p-CF3C6H4ZnCl
also exhibited good reactivity in the cross-coupling with
p-ClC6H4C(O)Ph, p-ClC6H4COOEt, p-ClC6H4C(O)NEt2 or
o-ClC6H4C(O)Ph. But the reaction with o-ClC6H4C(O)Ph
required higher catalyst loading (0.5 mol%) than the others
due to steric hindrance. A heteroarylzinc reagent, 2-furylzinc
chloride, was also tested. It showed a relatively low reactivity
although it is an electron-rich nucleophile. Its reaction with
p-ClC6H4CF3, p-ClC6H4C(O)Ph, p-ClC6H4COOEt or p-ClC6H4C-
(O)NEt2 gave excellent yields, but much higher catalyst load-
ings are necessary compared with p-MeC6H4ZnCl (entries
31–34, Table 4). Reaction of 2-furylzinc chloride with
o-ClC6H4CN was also carried out in the presence of 2 mol% 3a
at 90 °C, giving 71% product yield.
Table 3 Screening of reaction conditions of the cross-coupling cata-
lyzed by 3aa
Entry
Solvent
Temp. (°C)
Yieldb (%)
1
2
3
4
5
6
7
8
THF–NMP (1 : 1)
THF–NMP (2 : 1)
THF–DMA (2 : 1)
THF–DMA (2 : 1)
THF–DMA (2 : 1)
THF–toluene (1 : 1)
THF
Toluene
NMP
THF–NMP (2 : 1)
THF–NMP (2 : 1)
80
80
80
40
60
80
80
80
80
80
80
68
94
87
40
59
Trace
Trace
Trace
68
9
10
11
32c
2d
a Unless otherwise specified, the reactions were carried out on a
0.5 mmol scale according to the conditions indicated by the above
equation; 1.0 mmol p-MeC6H4ZnCl were employed. p-MeC6H4ZnCl was
prepared from ZnCl2 and an equiv. of p-MeC6H4MgBr in the presence
of two equiv. of LiCl. b Isolated yield. c p-MeC6H4ZnCl was prepared
from ZnCl2 and an equiv. of p-MeC6H4Li. d p-MeC6H4ZnCl was
prepared from ZnCl2 and an equiv. of p-MeC6H4MgBr.
Chart 2) were demonstrated to catalyze cross-coupling of aryl
fluorides with Grignard reagents.5q,6c,12 However, most of
them showed lower catalytic activity than complex 3a. The
combination of Ni(acac)2 and hydroxyphosphine ligand 6
(Chart 2) exhibited high activity which was attributed to a
Ni–Mg bimetallic cooperation.5j Activity of complex 3a is com-
parable with that of Ni(acac)2/6 combination. Hence complex
3a is one of the most active catalysts for the Kumada coupling
of aryl fluorides.
Aryl C–Cl bonds are weaker than aryl C–F bonds. Complex
3a was expected to effectively catalyze the activation of aryl
C–Cl bonds. However, preliminary test showed that complex 3a
was not very effective in catalyzing the Kumada coupling of
aryl chlorides under the same conditions as above. Further
test proved that it was a very effective catalyst for the Negishi
coupling of p-ClC6H4OMe with p-MeC6H4ZnCl in a mixed
solvent of THF and NMP at 80 °C (entries 1 and 2, Table 3). A
series of solvents or solvent combinations involving THF–
NMP, THF–DMA, THF–toluene, THF, toluene and NMP were
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Table 4 Cross-coupling of arylzinc chlorides with aryl chlorides cata-
lysed by 3aa
Table 4 (Contd.)
Entry
19
ArCl
Ar1
mol% 3a
Yieldb (%)
85
Entry
1
ArCl
Ar1
mol% 3a
Yieldb (%)
83
o-MeC6H4
1
p-MeC6H4
0.1
20
21
22
o-MeC6H4
o-MeC6H4
o-MeC6H4
0.05
0.01
0.01
96
99
91
2
3
p-MeC6H4
4
1
68c
95c
p-Me2NC6H4
23
p-MeC6H4
0.5
93
4
p-Me2NC6H4
p-MeOC6H4
p-MeC6H4
0.01
0.1
99
81
96
98
74
99
91
99
85
96
24
25
p-MeC6H4
p-MeC6H4
0.01
0.01
99
99
5
6
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
7
p-MeOC6H4
p-Me2NC6H4
p-MeC6H4
26
p-MeOC6H4
0.01
90
8
9
27
28
29
p-CF3C6H4
p-CF3C6H4
p-CF3C6H4
0.01
0.01
0.01
88
99
89
10
11
12
13
p-MeOC6H4
p-MeC6H4
p-MeOC6H4
p-MeC6H4
30
p-CF3C6H4
0.5
98
31
32
33
34
2-furyl
2-furyl
2-furyl
2-furyl
1
2
2
1
90
14
p-MeOC6H4
0.01
97
84d
92d
99
15
16
p-MeC6H4
p-MeC6H4
0.1
0.2
58
99
17
18
p-MeOC6H4
p-MeC6H4
0.5
0.5
73
92
35
2-furyl
2
71d
a Unless otherwise specified, the reactions were carried out on a
0.5 mmol scale according to the conditions indicated by the above
equation, 2.0 equiv. of ArZnCl were employed. b Isolated yield. c The
reaction was run at 100 °C. d The reaction was run at 90 °C.
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Compared with the reported catalysts for the Negishi coup- General procedure for the Kumada cross-coupling of
ling of aryl chlorides, the current catalyst exhibited aryl fluorides
lower activity than Buchwald’s ones, especially for the
ArMgBr (1.5 cm3, 0.5 M solution in THF, 0.75 mmol) was
bulky substrates.14 However, its activity is comparable
added into a Schlenk tube by syringe. The solvent was removed
to or higher than that of the reported nickel catalyst sys-
in vacuo. Toluene (2 cm3), complex 3a (1.2 mg, 0.0025 mmol)
and aryl fluorides (0.5 mmol) were respectively added. The
tems.5p,8c–e,15 In comparison with complexes 1 and 2a–2c, it
can be seen that a small adjustment of the ligand structure
mixture was stirred at 25 °C for 24 h. Water (10 cm3) and
results in marked changes in the catalytic properties. Complex
several drops of acetic acid were successively added. The
3a exhibits much higher activity than complexes 2a–2c in cata-
mixture was extracted with Et2O (3 × 10 cm3). The combined
organic phases were dried over anhydrous Na2SO4, concen-
lyzing aryl C–halide bond activation, but it is ineffective in
catalyzing the alkyl C–Cl bond activation. We expect further
trated by rotary evaporation, and purified by column chromato-
improvement of catalytic properties through the modification
graphy (silica gel).
of ligands.
General procedure for the Negishi cross-coupling of
aryl chlorides
A Schlenk tube was charged with aryl chloride (0.5 mmol),
Conclusions
NMP (1.05 cm3) and a solution of complex 3a (0.1 cm3, 0.0005
We synthesized three P,N,N-pincer nickel complexes (3a–3c)
and evaluated their catalysis in aryl C–F and C–Cl bond acti-
vation. Complex 3a effectively catalyzes cross-coupling of acti-
vated, unactivated and deactivated aryl fluorides and 2- or
3-fluoropyridines with aryl Grignard reagents, forming biaryls
in 54–99% yields. A series of aryl or heteroaryl chlorides were
also catalytically coupled with arylzinc reagents by 3a. The zinc
reagents used in the reactions include electron-rich and elec-
tron-poor substituted phenylzinc chlorides and 2-furylzinc
chloride. The reactions required low catalyst loadings in most
cases and tolerated functional groups including PhC(O),
COOEt, C(O)NEt2, CN and CF3 and nitrogen-containing hetero-
cycles. Compared with the reported catalyst systems, complex
3a is one of the most effective nickel catalysts for the Kumada
cross-coupling of aryl fluorides and the Negishi cross-coupling
of aryl chlorides.
M solution in THF, 0.00005 mmol). To the stirred mixture
ArZnCl solution (2.0 cm3, 0.5 M solution in THF, 1.0 mmol)
was added by syringe. The reaction mixture was stirred at
80 °C for 24 h. Water (10 mL) and several drops of hydrochloric
acid were successively added. The mixture was extracted with
Et2O (3 × 10 cm3). The combined organic phases were dried
over anhydrous Na2SO4, concentrated by rotary evaporation,
and purified by column chromatography (silica gel).
Product characterization
4-Methoxy-4′-methylbiphenyl.17 1H NMR (400 MHz, CDCl3):
δ 2.37 (s, 3H, Me), 3.83 (s, 3H, OMe), 6.95 (d, J = 8.8 Hz, 2H,
C6H4), 7.21 (d, J = 7.9 Hz, 2H, C6H4), 7.44 (d, J = 8.1 Hz, 2H,
C6H4), 7.50 (d, J = 8.8 Hz, 2H, C6H4). 13C NMR (101 MHz,
CDCl3): δ 21.18, 55.45, 114.29, 126.71, 128.08, 129.57, 133.87,
136.47, 138.10, 159.07.
3-Methoxy-4′-methylbiphenyl.18 1H NMR (300 MHz, CDCl3):
δ 2.35 (s, 3H, Me), 3.79 (s, 3H, OMe), 6.83 (d, J = 7.9 Hz, 1H,
C6H4), 7.10–7.32 (m, 5H, C6H4), 7.46 (d, J = 7.5 Hz, 2H, C6H4).
13C NMR (75 MHz, CDCl3): δ 21.18, 55.32, 112.49, 112.86,
Experimental section
The reactions were performed under a nitrogen atmosphere 119.60, 127.12, 129.56, 129.80, 137.27, 138.35, 142.81, 160.09.
using standard Schlenk and vacuum line techniques. THF and NMR
4′-Methyl-N,N-dimethylbiphenyl-4-amine.19 1H
Et2O were distilled under nitrogen over sodium/benzophenone (400 MHz, CDCl3): δ 2.26 (s, 3H, Me), 2.85 (s, 6H, NMe2), 6.68
and degassed prior to use. Toluene was distilled under nitro- (d, J = 8.8 Hz, 2H, C6H4), 7.09 (d, J = 7.9 Hz, 2H, C6H4), 7.35 (d,
gen over sodium and degassed prior to use. NMP and DMA J = 8.2 Hz, 2H, C6H4), 7.38 (d, J = 8.9 Hz, 2H, C6H4). 13C NMR
were dried over 4 Å molecular sieves, fractionally distilled (101 MHz, CDCl3): δ 21.17, 40.77, 112.97, 126.31, 127.65,
under reduced pressure and stored under a nitrogen atmos- 129.47, 129.50, 135.74, 138.51, 149.95.
phere. Grignard reagents were prepared according to literature
3,4-Dimethoxy-4′-methylbiphenyl.5q 1H NMR (400 MHz,
procedures.16 Arylzinc chlorides were prepared from ZnCl2 and CDCl3): δ 2.38 (s, 3H, Me), 3.91 (s, 3H, OMe), 3.93 (s, 3H,
an equiv. of ArMgBr in the presence of 2 equiv. of LiCl. All OMe), 6.92 (d, J = 8.2 Hz, 1H, C6H3), 7.09–7.13 (m, 2H, C6H3),
other solvents and reagents were used as received. NMR 7.22 (d, J = 7.9 Hz, 2H, C6H4), 7.45 (d, J = 8.1 Hz, 2H, C6H4).
spectra were determined on a Bruker av300 or a Bruker Avance 13C NMR (101 MHz, CDCl3): δ 21.16, 56.02, 56.08, 110.46,
III 400 NMR spectrometer at room temperature. The chemical 111.60, 119.27, 126.80, 129.54, 134.34, 136.67, 138.29, 148.51,
shifts of the 1H NMR spectra were referenced to TMS or 149.22.
solvent residual signal; the chemical shifts of the 13C NMR
3′,4′-Dimethoxy-N,N-dimethylbiphenyl-4-amine.5q 1H NMR
spectra were referenced to internal solvent resonances. HR-MS (400 MHz, CDCl3): δ 2.98 (s, 6H, NMe), 3.90 (s, 3H, OMe), 3.94
data were recorded on an Agilent 6890/Micromass LCT-MS (s, 3H, OMe), 6.80 (d, J = 8.8 Hz, 2H, C6H4), 6.91 (d, J = 8.1 Hz,
spectrometer (EI).
1H, C6H3), 7.06–7.11 (m, 2H, C6H3), 7.46 (d, J = 8.5 Hz, 2H,
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C6H4). 13C NMR (101 MHz, CDCl3): δ 40.77, 55.99, 56.09,
2-(4-Methoxyphenyl)pyridine.3h 1H NMR (400 MHz, CDCl3):
109.99, 111.65, 112.96, 118.54, 127.55, 129.41, 134.59, 147.80, δ 3.84 (s, 3H, OMe), 6.99 (d, J = 8.9 Hz, 2H, C6H4), 7.13–7.16
149.17, 149.83.
(m, 1H, Py), 7.63–7.70 (m, 2H, Py), 7.95 (d, J = 8.9 Hz, 2H,
1-Isopropyl-3-(4′-methylbiphenyl-4-yl)-1H-indole. 1H NMR C6H4), 8.64 (d, J = 4.7 Hz, 1H, Py). 13C NMR (101 MHz, CDCl3):
(400 MHz, CDCl3): δ 1.58 (d, J = 6.7 Hz, 6H, Me), 2.40 (s, 3H, δ 55.41, 114.20, 119.87, 121.48, 128.24, 132.11, 136.73, 149.61,
Me), 4.72 (sept, J = 6.7 Hz, 1H, CH), 7.19 (t, J = 7.4 Hz, 1H, Ar), 157.18, 160.54.
7.25–7.29 (m, 3H, Ar), 7.41–7.45 (m, 2H, Ar), 7.56 (d, J = 8.0 Hz,
N,N-Dimethyl-(4-pyridin-2-yl)benzenamine.21 1H
NMR
2H, Ar), 7.66 (d, J = 8.2 Hz, 2H, Ar), 7.73 (d, J = 8.3 Hz, 2H, Ar), (400 MHz, CDCl3): δ 3.02 (s, 6H, NMe), 6.80 (d, J = 9.0 Hz, 2H,
7.99 (d, J = 7.9 Hz, 1H, Ar). 13C NMR (101 MHz, CDCl3): C6H4), 7.08–7.11 (m, 1H, Py), 7.62–7.69 (m, 2H, Py), 7.92 (d, J =
δ 21.26, 22.98, 47.26, 109.91, 116.64, 120.07, 120.21, 121.65, 9.0 Hz, 2H, C6H4), 8.61–8.62 (m, 1H, Py). 13C NMR (101 MHz,
121.86, 126.40, 126.90, 127.38, 127.68, 129.63, 134.85, 136.55, CDCl3): δ 40.52, 112.38, 119.28, 120.72, 127.38, 127.84, 136.60,
136.90, 138.36, 138.46. HR-MS (EI): m/z = 325.1823, calcd for 149.53, 151.20, 157.73.
C24H23N: 325.1830.
4-Methyl-2-p-tolylpyridine.22 1H NMR (400 MHz, CDCl3):
(4′-Methylbiphenyl-4-yl)methanol.5q 1H NMR (400 MHz, δ 2.38 (s, 3H, Me), 2.39 (s, 3H, Me), 7.00 (d, J = 5.0 Hz, 1H,
CDCl3): δ 1.66 (t, J = 5.9 Hz, 1H, OH), 2.40 (s, 3H, Me), 4.74 pyridine), 7.26 (d, J = 8.0 Hz, 2H, C6H4), 7.50 (s, 1H,
(d, J = 5.8 Hz, 2H, CH2), 7.25 (d, J = 8.1 Hz, 2H, C6H4), 7.43 (d, pyridine), 7.87 (d, J = 8.2 Hz, 2H, C6H4), 8.52 (d, J = 5.0 Hz, 1H,
J = 8.1 Hz, 2H, C6H4), 7.49 (d, J = 8.1 Hz, 2H, C6H4), 7.58 (d, pyridine). 13C NMR (101 MHz, CDCl3):
δ 21.30, 21.34,
J = 8.1 Hz, 2H, C6H4). 13C NMR (101 MHz, CDCl3): δ 21.24, 121.28, 122.93, 126.87, 129.50, 136.82, 138.84, 147.71, 149.43,
65.31, 127.07, 127.28, 127.60, 129.65, 137.27, 138.07, 139.71, 157.44.
140.74.
3-p-Tolylpyridine.23 1H NMR (300 MHz, CDCl3): δ 2.39 (s,
(4′-N,N-Dimethylaminobiphenyl-4-yl)methanol.5q 1H NMR 3H, Me), 7.28 (b, 3H, Ar), 7.46 (b, 2H, Ar), 7.82 (b, 1H, Ar), 8.55
(400 MHz, CDCl3): δ 1.63 (t, J = 6.0 Hz, 1H, OH), 3.00 (s, 6H, (b, 1H, Ar), 8.83 (b, 1H, Ar). 13C NMR (101 MHz, CDCl3):
NMe), 4.72 (d, J = 5.9 Hz, 2H, CH2), 6.81 (d, J = 8.8 Hz, 2H, δ 21.25, 123.63, 127.07, 129.91, 134.26, 135.00, 136.69, 138.14,
C6H4), 7.40 (d, J = 8.2 Hz, 2H, C6H4), 7.51 (d, J = 8.9 Hz, 2H, 148.23, 148.25.
C6H4), 7.56 (d, J = 8.2 Hz, 2H, C6H4). 13C NMR (101 MHz,
1,4-Di(p-methylphenyl)benzene.8d 1H NMR (400 MHz,
CDCl3): δ 40.72, 65.41, 112.92, 126.55, 127.65, 127.78, 128.92, CDCl3): δ 2.41 (s, 6H, Me), 7.27 (d, J = 6.7 Hz, 4H, C6H4), 7.54
138.65, 140.84, 150.16.
(d, J = 7.9 Hz, 4H, C6H4), 7.65 (s, 4H, C6H4). 13C NMR
NMR (101 MHz, CDCl3): δ 21.27, 127.01, 127.40, 129.67, 137.22,
2′-Methyl-N,N-dimethylbiphenyl-4-amine.19 1H
(400 MHz, CDCl3): δ 2.31 (s, 3H, Me), 2.98 (s, 6H, NMe), 6.78 138.03, 139.92.
(d, J = 8.8 Hz, 2H, C6H4), 7.18–7.25 (m, 6H, C6H4). 13C NMR
1,3,5-Tris(p-methylphenyl)benzene.5j 1H NMR (400 MHz,
(101 MHz, CDCl3): δ 20.81, 40.74, 112.22, 125.85, 126.64, CDCl3): δ 2.45 (s, 9H, Me), 7.32 (d, J = 7.9 Hz, 6H, C6H4), 7.63
130.07, 130.21, 130.40, 135.65, 142.14. 149.52.
(d, J = 8.1 Hz, 6H, C6H4), 7.77 (s, 3H, C6H3). 13C NMR
N,N-Dimethylbiphenyl-4-amine.8c 1H NMR (400 MHz, (101 MHz, CDCl3): δ 21.27, 124.70, 127.32, 129.67, 137.39,
CDCl3): δ 2.99 (s, 6H, NMe), 6.80 (d, J = 8.8 Hz, 2H, C6H4), 138.53, 142.30.
7.23–7.27 (m, 1H, C6H5), 7.39 (t, J = 7.7 Hz, 2H, C6H5), 7.50 (d,
1-Methoxy-2-(p-toyl)benzoate.8d 1H
NMR
(400
MHz,
J = 8.8 Hz, 2H, C6H4), 7.55 (d, J = 7.3 Hz, 2H, C6H5). 13C NMR CDCl3): δ 2.38 (s, 3H, Me), 3.79 (s, 3H, OMe), 6.96 (d, J =
(101 MHz, CDCl3): δ 40.73, 112.92, 126.12, 126.43, 127.84, 8.4 Hz, 1H, C6H4), 6.98–7.04 (m, 1H, C6H4), 7.21 (d, J = 7.9 Hz,
128.78, 129.41, 141.37, 150.12.
2H, C6H4), 7.27–7.31 (m, 1H, C6H4), 7.42 (d, J = 8.1 Hz, 2H,
N,N-Dimethyl-(4-naphthalen-1-yl)aniline.20 1H
NMR C6H4). 13C NMR (101 MHz, CDCl3): δ 21.34, 55.65, 111.30,
(400 MHz, CDCl3): δ 2.90 (s, 6H, NMe), 6.74 (d, J = 8.6 Hz, 2H, 120.92, 128.49, 128.86, 129.53, 130.83, 130.92, 135.73, 136.72,
C6H4), 7.30 (t, J = 8 Hz, Ar), 7.33–7.40 (m, 2H, Ar), 7.69 (d, J = 156.63.
8.1 Hz, 1H, Ar), 7.77 (d, J = 7.9 Hz, 1H, Ar), 7.93 (d, J = 8.3 Hz,
N,N,2′,5′-Tetramethylbiphenyl-4-amine.24 1H NMR (400 MHz,
1H, Ar). 13C NMR (101 MHz, CDCl3): δ 40.72, 112.38, 125.61, CDCl3): δ 2.27 (s, 3H, Me), 2.33 (s, 3H, Me), 2.99 (s, 6H, NMe2),
125.70, 125.82, 126.46, 126.87, 126.96, 128.33, 128.87, 130.93, 6.78 (d, J = 8.8 Hz, 2H, C6H4), 7.00–7.07 (m, 2H, C6H3), 7.14 (d,
132.09, 134.06, 140.62, 149.91.
J = 7.6 Hz, 1H, C6H3), 7.22 (d, J = 8.8 Hz, 2H, C6H4). 13C NMR
4′-Methyl-4-(trifluoromethyl)biphenyl.8d 1H NMR (400 MHz, (101 MHz, CDCl3): δ 20.31, 21.08, 40.77, 112.23, 127.34,
CDCl3): 2.45 (s, 3H, Me), 7.31 (d, J = 8.0 Hz, 2H, C6H4), 7.53 (d, 130.04, 130.34, 130.82, 132.46, 135.21, 141.92, 149.46.
J = 8.1 Hz, 2H, C6H4), 7.70 (s, 4H, C6H4). 13C NMR (101 MHz,
4-Methoxybiphenyl.25 1H NMR (400 MHz, CDCl3): δ 3.87 (s,
CDCl3): δ 21.26, 124.51 (q, J = 272.7 Hz), 125.80 (q, J = 4.0 Hz), 3H, OMe), 7.00 (d, J = 8.8 Hz, 2H, Ar), 7.30–7.35 (m, 1H, Ar),
127.24, 127.30, 129.17 (q, J = 32.3 Hz), 129.85, 136.99, 138.30, 7.42–7.46 (m, 2H, Ar), 7.54–7.59 (m, 4H, Ar). 13C NMR
144.77.
(101 MHz, CDCl3): δ 55.47, 114.34, 126.79, 126.87, 128.29,
2-p-Tolylpyridine.17 1H NMR (300 MHz, CDCl3): δ 2.38 (s, 128.86, 133.92, 140.97, 159.29.
3H, Me), 7.13–7.17 (m, 1H, Py), 7.26 (d, J = 7.8 Hz, 2H, C6H4),
4′-Methoxy-4-(trifluoromethyl)biphenyl.26 1H NMR (400 MHz,
7.66–7.67 (m, 2H, Py), 7.89 (d, J = 8.0 Hz, 2H, C6H4), 8.65–8.66 CDCl3): δ 3.87 (s, 3H, OMe), 7.01 (d, J = 8.8 Hz, 2H, C6H4), 7.55
(m, 1H, Py). 13C NMR (75 MHz, CDCl3): δ 21.30, 120.25, (d, J = 8.8 Hz, 2H, C6H4), 7.66 (s, 4H, C6H4). 13C NMR
121.82, 126.83, 129.53, 136.68, 136.70, 138.96, 149.64, 157.52.
(101 MHz, CDCl3): δ 55.52, 114.58, 124.53 (q, J = 273 Hz),
6420 | Org. Biomol. Chem., 2014, 12, 6414–6424
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125.82 (q, J = 4.0 Hz), 127.01, 128.50, 128.84 (q, J = 32.3 Hz),
(4′-Methylbiphenyl-2-yl)(phenyl)methanone.34 1H
NMR
132.33, 144.44, 160.00.
(400 MHz, CDCl3): δ 2.25 (s, 3H, Me), 7.01 (d, J = 7.8 Hz, 2H,
Dimethyl-(4′-trifluoromethylbiphenyl-4-yl)-amine.27 1H NMR C6H4), 7.15 (d, J = 8.1 Hz, 2H, C6H4), 7.29 (t, J = 7.7 Hz, 2H,
(400 MHz, CDCl3): δ 3.02 (s, 6H, NMe), 6.81 (d, J = 8.8 Hz, 2H, Ph), 7.39–7.50 (m, 4H, Ar), 7.54–7.59 (m, 1H, Ar), 7.66–7.69
C6H4), 7.53 (d, J = 8.9 Hz, 2H, C6H4), 7.64 (s, 4H, C6H4). 13C (m, 2H, Ar). 13C NMR (101 MHz, CDCl3): δ 21.28, 126.88,
NMR (101 MHz, CDCl3): δ 21.27, 124.52 (q, J = 272.9 Hz), 128.22, 128.82, 128.97, 129.14, 130.11, 130.23, 130.41, 132.92,
125.81(q, J = 3.8 Hz), 127.25, 127.31, 129.19 (q, J = 32.5 Hz), 137.17, 137.42, 137.56, 139.03, 141.30, 198.96.
129.85, 137.01, 138.30, 144.79.
(4′-Methoxybiphenyl-2-yl)(phenyl)methanone.35 1H
NMR (400 MHz, CDCl3): δ 3.69 (s, 3H, OMe), 6.72 (d, J = 8.8 Hz, 2H,
NMR
(4′-Methylbiphenyl-4-yl)(phenyl)methanone.28 1H
(400 MHz, CDCl3): δ 2.41 (s, 3H, Me), 7.29 (d, J = 7.9 Hz, 2H, C6H4), 7.17 (d, J = 8.8 Hz, 2H, C6H4), 7.26 (t, J = 7.6 Hz, 2H,
C6H4), 7.50 (t, J = 7.5 Hz, 2H, Ph), 7.55 (d, J = 8.1 Hz, 2H, Ph), C6H5), 7.36–7.49 (m, 4H, Ar), 7.50–7.56 (m, 1H, Ar), 7.63–7.65
7.59 (t, J = 7.4 Hz, 1H, Ph), 7.69 (d, J = 8.4 Hz, 2H, C6H4), 7.83 (m, 2H, Ar). 13C NMR (101 MHz, CDCl3): δ 55.23, 113.85,
(d, J = 8.4 Hz, 2H, C6H4), 7.88 (d, J = 8.3 Hz, 2H, C6H4). 13C 126.71, 128.18, 128.74, 129.97, 130.04, 130.19, 130.37, 132.73,
NMR (101 MHz, CDCl3): δ 21.31, 126.84, 127.27, 128.43, 132.91, 137.46, 138.93, 140.77, 159.03, 199.05.
129.84, 130.12, 130.88, 132.45, 136.09, 137.21, 137.99, 138.32,
145.33, 196.49.
4′-Methylbiphenyl-2-carbonitrile.5q 1H NMR (400 MHz,
CDCl3): δ 2.42 (s, 3H, Me), 7.30 (d, J = 8.1 Hz, 2H, C6H4), 7.42
(4′-Methoxybiphenyl-4-yl)(phenyl)methanone.29 1H
NMR (td, J = 1.3, 7.6 Hz, 1H, C6H4), 7.46 (d, J = 8.1 Hz, 2H, C6H4),
(400 MHz, CDCl3): δ 3.87 (s, 3H, OMe), 7.02 (d, J = 8.8 Hz, 2H, 7.49–7.52 (m, 1H, C6H4), 7.63 (td, J = 1.4, 7.7 Hz, 1H, C6H4),
C6H4), 7.50 (t, J = 7.6 Hz, 2H, C6H5), 7.58–7.62 (m, 3H, C6H5 + 7.74–7.76 (m, 1H, C6H4). 13C NMR (101 MHz, CDCl3): δ 21.38,
C6H4), 7.67 (d, J = 8.3 Hz, 2H, C6H4), 7.82–7.84 (m, 2H, C6H5), 111.35, 119.00, 127.40, 128.75, 129.58, 130.11, 132.88, 133.85,
7.88 (d, J = 8.3 Hz, 2H, C6H4). 13C NMR (101 MHz, CDCl3): δ 135.41, 138.83, 146.68.
55.52, 114.55, 126.51, 128.42, 128.53, 130.11, 130.94, 132.42,
132.47, 135.71, 138.00, 144.98, 160.01, 196.48.
4′-Methoxy-2-methylbiphenyl.36 1H NMR (400 MHz, CDCl3):
δ 2.35 (s, 3H, Me), 3.91 (s, 3H, OMe), 7.02 (d, J = 8.7 Hz, 2H,
Ethyl 4′-methylbiphenyl-4-carboxylate.30 1H NMR (400 MHz, C6H4), 7.29–7.33 (m, 6H, C6H4). 13C NMR (101 MHz, CDCl3):
CDCl3): δ 1.42 (t, J = 7.1 Hz, 3H, Et), 2.41 (s, 3H, Me), 4.40 (q, δ 20.66, 55.35, 113.61, 125.87, 127.09, 130.02, 130.36, 130.41,
J = 7.1 Hz, 2H, Et), 7.28 (d, J = 7.9 Hz, 2H, C6H4), 7.53 (d, J = 134.49, 135.57, 141.67, 158.64.
8.1 Hz, 2H, C6H4), 7.65 (d, J = 8.5 Hz, 2H, C6H4), 8.10 (d, J =
(2′-Methylbiphenyl-4-yl)(phenyl)methanone.8c 1H
NMR
8.6 Hz, 2H, C6H4). 13C NMR (101 MHz, CDCl3): δ 14.51, 21.30, (400 MHz, CDCl3): δ 2.31 (s, 3H, Me), 7.26–7.30 (m, 4H, Ar),
61.06, 126.88, 127.24, 129.06, 129.77, 130.17, 137.27, 138.20, 7.45 (d, J = 8.3 Hz, 2H, Ar), 7.51 (t, J = 7.5 Hz, 2H, Ar), 7.61 (t,
145.59, 166.71.
J = 7.4 Hz, 1H, Ar), 7.85–7.88 (m, 4H, Ar). 13C NMR (101 MHz,
Ethyl4′-methoxybiphenyl-4-carboxylate.31 1HNMR(400MHz, CDCl3): δ 20.59, 126.09, 128.02, 128.46, 129.33, 129.73, 130.17,
CDCl3): δ 1.42 (t, J = 7.1 Hz, 3H, Et), 3.86 (s, 3H, OMe), 4.40 (q, 130.18, 130.69, 132.52, 135.38, 136.12, 137.89, 140.99, 146.52,
J = 7.1 Hz, 2H, Et), 7.00 (d, J = 8.8 Hz, 2H, C6H4), 7.57 (d, J = 196.63.
8.8 Hz, 2H, C6H4), 7.62 (d, J = 8.5 Hz, 2H, C6H4), 8.09 (d, J =
Ethyl 2′-methylbiphenyl-4-carboxylate.17 1H NMR (400 MHz,
8.5 Hz, 2H, C6H4). 13C NMR (101 MHz, CDCl3): δ 14.47, 55.45, CDCl3): δ 1.41 (t, J = 7.1 Hz, 3H, Et), 2.26 (s, 3H, Me), 4.41 (q,
61.00, 114.45, 126.51, 128.44, 128.67, 130.16, 132.51, 145.17, J = 7.1 Hz, 2H, Et), 7.20–7.29 (m, 4H, C6H4), 7.39 (d, J = 8.5 Hz,
159.90, 166.67.
2H, C6H4), 8.09 (d, J = 8.5 Hz, 2H, C6H4). 13C NMR (101 MHz,
N,N-Diethyl-4′-methylbiphenyl-4-carboxamide.8c 1H
NMR CDCl3): δ 14.51, 20.51, 61.09, 126.03, 127.94, 129.06, 129.35,
(400 MHz, CDCl3): δ 1.21 (b, 6H, Et), 2.40 (s, 3H, Me), 3.32 (b, 129.50, 129.66, 130.61, 135.30, 141.03, 146.76, 166.70.
2H, Et), 3.57 (b, 2H, Et), 7.26 (d, J = 7.9 Hz, 2H, C6H4), 7.44 (d,
N,N-Diethyl-2′-methylbiphenyl-4-carboxamide.8c 1H
NMR
J = 8.5 Hz, 2H, C6H4), 7.50 (d, J = 8.1 Hz, 2H, C6H4), 7.60 (d, J = (400 MHz, CDCl3): δ 1.17 (b, 3H, Et), 1.27 (b, 3H, Et), 2.27 (s,
8.5 Hz, 2H, C6H4). 13C NMR (101 MHz, CDCl3): δ 13.06, 14.38, 3H, Me), 3.35 (b, 2H, Et), 3.58 (b, 2H, Et), 7.21–7.28 (m, 4H,
39.45, 43.49, 55.47, 114.42, 126.71, 126.98, 128.26, 132.99, C6H4), 7.35 (d, J = 8.2 Hz, 2H, C6H4), 7.43 (d, J = 8.2 Hz, 2H,
135.55, 141.72, 159.57, 171.34.
C6H4). 13C NMR (101 MHz, CDCl3): δ 13.04, 14.40, 20.55, 39.34,
N,N-Diethyl-4′-Methoxybiphenyl-4-carboxamide.32 1H NMR 43.46, 125.93, 126.28, 127.63, 127.93, 128.78, 129.31, 129.79,
(400 MHz, CDCl3): δ 1.21 (b, 6H, Et), 3.33 (b, 2H, Et), 3.55 (b, 130.52, 135.40, 135.74, 141.23, 142.94, 171.34.
2H, Et), 3.85 (s, 3H, OMe), 6.98 (d, J = 8.8 Hz, 2H, C6H4), 7.42
2-p-Tolyl-nicotinonitrile.37 1H NMR (400 MHz, CDCl3):
(d, J = 8.0 Hz, 2H, C6H4), 7.53 (d, J = 8.9 Hz, 2H, C6H4), 7.57 (d, δ 2.44 (s, 3H, Me), 7.33–7.36 (m, 3H, C6H4 + Py), 7.84 (d, J =
J = 8.1 Hz, 2H, C6H4). 13C NMR (101 MHz, CDCl3): δ 13.08, 8.2 Hz, 2H, C6H4), 8.05 (dd, J = 1.7, 7.9 Hz, 1H, Py), 8.85 (dd,
14.33, 21.21, 39.34, 43.40, 126.93, 126.97, 127.04, 129.67, J = 1.7, 4.8 Hz, 1H, Py). 13C NMR (101 MHz, CDCl3): δ 21.54,
135.88, 137.60, 142.03, 171.29.
107.35, 117.96, 121.36, 128.92, 129.55, 134.51, 140.67, 141.95,
4′-Methylbiphenyl-4-carbonitrile.33 1H NMR (400 MHz, 152.73, 161.19.
CDCl3): δ 2.42 (s, 3H, Me), 7.29 (d, J = 8 Hz, 2H, C6H4), 7.49 (d,
2-Methoxy-6-p-tolylpyridine.38 1H NMR (400 MHz, CDCl3):
J = 8 Hz, 2H, C6H4), 7.67 (d, J = 8.6 Hz, 2H, C6H4), 7.71 (d, J = δ 2.40 (s, 3H, Me), 4.03 (s, 3H, OMe), 6.66 (d, J = 8.2 Hz, 1H,
8.6 Hz, 2H, C6H4). 13C NMR (101 MHz, CDCl3): δ 21.33, 110.66, Py), 7.26 (d, J = 7.3 Hz, 2H, C6H4), 7.31 (d, J = 7.4 Hz, 1H, Py),
119.19, 127.19, 127.60, 129.97, 132.71, 136.40, 138.89, 145.74.
7.60 (dd, J = 7.5, 8.1 Hz, 1H, Py), 7.94 (d, J = 8.2 Hz, 2H, C6H4).
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13C NMR (101 MHz, CDCl3): δ 21.42, 53.31, 108.93, 112.55, 8.6 Hz, 2H, C6H4), 7.78–7.82 (m, 2H, Ph), 7.85 (d, J = 8.6 Hz,
126.71, 129.45, 136.45, 138.93, 139.23, 154.85, 163.80.
2H, C6H4). 13C NMR (101 MHz, CDCl3): δ 107.51, 112.23,
2-(4-Methylphenyl)-4-methylquinoline.39 1H NMR (400 MHz, 123.46, 128.44, 130.07, 130.98, 132.46, 134.56, 136.01, 137.91,
CDCl3): δ 2.44 (s, 3H, Me), 2.76 (s, 3H, Me), 7.33 (d, J = 7.9 Hz, 143.39, 153.02, 196.18.
2H, C6H4), 7.51–7.55 (m, 1H, quinolyl), 7.69–7.73 (m, 2H,
Ethyl 4-(furan-2-yl)benzoate.8c 1H NMR (400 MHz, CDCl3):
quinolyl), 7.98–8.00 (m, 1H, quinolyl), 8.06 (d, J = 8.2 Hz, 2H, δ 1.41 (t, J = 7.1 Hz, 3H, Et), 4.38 (q, J = 7.1 Hz, 2H, Et), 6.51
C6H4), 8.21–8.13 (m, 1H, quinolyl). 13C NMR (101 MHz, (dd, J = 1.8, 3.4 Hz, 1H, furyl), 6.79 (d, J = 3.4 Hz, 1H, furyl),
CDCl3): δ 19.16, 21.48, 119.74, 123.73, 125.96, 127.33, 127.54, 7.52 (d, J = 1.7 Hz, 1H, furyl), 7.72 (d, J = 8.6 Hz, 2H, C6H4),
129.38, 129.65, 130.36, 137.15, 139.37, 144.76, 148.30, 157.18.
8.06 (d, J = 8.6 Hz, 2H, C6H4). 13C NMR (101 MHz, CDCl3):
2-(4-Methoxyphenyl)-4-methylquinoline.40 1H NMR (400 MHz, δ 14.50, 61.10, 107.30, 112.15, 123.50, 129.03, 130.21, 134.80,
CDCl3): δ 2.75 (s, 3H, Me), 3.89 (s, 3H, OMe), 7.04 (d, J = 143.23, 153.11, 166.49.
8.8 Hz, 2H, C6H4), 7.50–7.54 (m, 1H, quinolyl), 7.68–7.72 (m,
N,N-Diethyl-4-(furan-2-yl)carboxamide. 1H NMR (400 MHz,
2H, quinolyl), 7.97 (d, J = 8.3 Hz, 1H, quinolyl), 8.12–8.15 (m, CDCl3): δ 1.12 (b, 3H, Et), 1.24 (b, 3H, Et), 3.28 (b, 2H, Et), 3.54
3H, C6H4 + quinolyl). 13C NMR (101 MHz, CDCl3): δ 19.17, (b, 2H, Et), 6.47 (dd, J = 1.8, 3.4 Hz, 1H, furyl), 6.69 (d, J =
55.52, 114.28, 119.42, 123.72, 125.79, 127.13, 128.96, 129.37, 3.4 Hz, 1H, furyl), 7.39 (d, J = 8.4 Hz, 2H, C6H4), 7.47 (d, J =
130.19, 132.51, 144.70, 148.27, 156.75, 160.82.
1.2 Hz, 1H, furyl), 7.68 (d, J = 8.4 Hz, 2H, C6H4). 13C NMR
(4′-(Trifluoromethyl)biphenyl-4-yl)(phenyl)methanone.41 1H (101 MHz, CDCl3): δ 13.02, 14.32, 39.41, 43.43, 105.95, 111.90,
NMR (400 MHz, CDCl3): δ 7.51 (t, J = 7.6 Hz, 2H, Ph), 7.62 (t, 123.72, 126.98, 131.65, 135.97, 142.60, 153.30, 171.06. HR-MS
J = 7.4 Hz, 1H, Ph), 7.72 (d, J = 8.4 Hz, 2H, C6H4), 7.75 (s, 4H, (EI): m/z = 243.1252, calcd for C15H17NO2: 243.1259.
C6H4), 7.83–7.86 (m, 2H, Ph), 7.92 (d, J = 8.4 Hz, 2H, C6H4).
2-Furan-2-yl-benzonitrile. 1H NMR (400 MHz, CDCl3): δ 6.56
13C NMR (101 MHz, CDCl3): δ 124.29 (q, J = 273.7 Hz), 126.06 (dd, J = 1.8, 3.5 Hz, 1H, furyl), 7.31 (d, J = 3.1 Hz, 1H, furyl),
(q, J = 4.0 Hz), 127.32, 127.77, 128.52, 130.16, 130.33 (q, J = 7.34 (dd, J = 1.1, 7.7 Hz, 1H, C6H4), 7.56 (d, J = 1.7 Hz, 1H,
32.3 Hz), 130.93, 132.71, 137.27, 137.65 143.66, 143.72, 196.27. furyl), 7.62 (td, J = 1.3, 8.1 Hz, 1H, C6H4), 7.70 (dd, J = 1.0,
Ethyl 4′-(trifluoromethyl)biphenyl-4-carboxylate.42 1H NMR 7.8 Hz, 1H, C6H4), 7.89 (d, J = 8.1 Hz, 1H, C6H4). 13C NMR
(400 MHz, CDCl3): δ 1.42 (t, J = 7.1 Hz, 3H, Et), 4.42 (q, J = (101 MHz, CDCl3): δ 106.96, 110.58, 112.40, 119.16, 126.05,
7.1 Hz, 2H, Et), 7.66 (d, J = 8.5 Hz, 2H, C6H4), 7.72 (s, 4H, 127.24, 133.08, 133.35, 134.28, 143.46, 149.88. HR-MS (EI): m/z
C6H4), 8.14 (d, J = 8.5 Hz, 2H, C6H4). 13C NMR (101 MHz, = 169.0520, calcd for C11H7NO: 169.0528.
CDCl3): δ 14.45, 61.26, 124.28 (q, J = 272.7 Hz), 125.98 (q, J =
4.0 Hz), 127.32, 127.73, 130.23 (q, J = 32.3 Hz), 130.28, 130.35,
143.68, 144.05, 166.38.
Acknowledgements
N,N-Diethyl-4′-(trifluoromethyl)biphenyl-4-carboxamide. 1H
NMR (400 MHz, CDCl3): δ 1.16 (b, 3H, Et), 1.26 (b, 3H, Et), This research was supported by the National Basic Research
3.32 (b, 2H, Et), 3.57 (b, 2H, Et), 7.48 (d, J = 8.3 Hz, 2H, C6H4), Program of China (grant no. 2009CB825300) and the National
7.62 (d, J = 8.3 Hz, 2H, C6H4), 7.70 (s, 4H, C6H4). 13C NMR Natural Science Foundation of China (grant no. 21172208).
(101 MHz, CDCl3): δ 13.06, 14.47, 39.48, 43.46, 124.35 (q, J = Authors thank Professor S.-M. Zhou for the crystal structure
272.7 Hz), 125.95 (q, J = 4.0 Hz), 127.19, 127.46, 127.57, 129.88 determination.
(q, J = 32.3 Hz), 137.21, 140.63, 144.04, 170.93. HR-MS (EI): m/z
= 321.1335, calcd for C18H18F3NO: 321.1340.
(4′-(Trifluoromethyl)biphenyl-2-yl)(phenyl)methanone.43 1H
NMR (400 MHz, CDCl3): δ 7.32 (t, J = 7.8 Hz, 2H, Ar), 7.38 (d,
Notes and references
J = 8.0 Hz, 2H, C6H4), 7.44–7.55 (m, 6H, Ar), 7.59–7.63 (m, 1H,
Ar), 7.66–7.68 (m, 2H, Ar). 13C NMR (101 MHz, CDCl3):
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